The terminal differentiation of embryonic muscle cells in culture is characterized by cell fusion to form multinucleated myotubes, cessation of DNA synthesis, withdrawal from the cell cycle, and production of muscle specific proteins and acetylcholine receptors. Cell surface glycoproteins are thought to be important components of cell-cell recognition and interaction. It has been proposed that interactions of glycoproteins may be the basis of cell fusion and other intercellular interactions. The role of surface glycoproteins in cell fusion has been evaluated. We have shown that inhibiting the glycosylation of surface glycoproteins blocks myoblast fusion and the expression of the acetylcholine receptor on the cell surface. Both phenomena are restored when glycosylation is blocked by the protesase inhibitor, leupeptin. These results show that: (1) The protein - but not the carbohydrate - moiety of some presently unknown glycoprotein is required for cell fusion. (2) The carbohydrate moiety of acetycholine receptor and the fusion protein(s) is required to stabilize both against proteolysis. (3) The carbohydrate moiety is not required for intracellular processing and export of either protein during embryonic muscle cell differentiation.